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Microfabricated Porous Silk Scaffolds for Vascularizing Engineered Tissues

机译：用于制造工程组织的微细多孔丝支架。

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摘要

There is critical clinical demand for tissue-engineered (TE), 3D constructs for tissue repair and organ replacements. Current efforts toward this goal are prone to necrosis at the core of larger constructs because of limited oxygen and nutrient diffusion. Therefore, critically sized 3D TE constructs demand an immediate vascular system for sustained tissue function upon implantation. To address this challenge the goal of this project was to develop a strategy to incorporate microchannels into a porous silk TE scaffold that could be fabricated reproducibly using microfabrication and soft lithography. Silk is a suitable biopolymer material for this application because it is mechanically robust, biocompatible, slowly degrades in vivo, and has been used in a variety of TE constructs. Here, the fabrication of a silk-based TE scaffold that contains an embedded network of porous microchannels is reported. Enclosed porous microchannels support endothelial lumen formation, a critical step toward development of the vascular niche, while the porous scaffold surrounding the microchannels supports tissue formation, demonstrated using human mesenchymal stem cells. This approach for fabricating vascularized TE constructs is advantageous compared to previous systems, which lack porosity and biodegradability or degrade too rapidly to sustain tissue structure and function. The broader impact of this research will enable the systemic study and development of complex, critically-sized engineered tissues, from regenerative medicine to in vitro tissue models of disease states.
机译：对于组织工程（TE），用于组织修复和器官置换的3D构造的临床需求非常关键。由于有限的氧气和养分扩散，目前为实现这一目标而进行的努力倾向于在较大结构的核心发生坏死。因此，临界尺寸的3D TE构造需要即时的血管系统以在植入后维持组织的功能。为了应对这一挑战，该项目的目标是开发一种将微通道整合到多孔丝TE支架中的策略，该支架可以使用微加工和软光刻技术可重复生产。丝绸是一种适合此应用的生物聚合物材料，因为它具有机械坚固性，生物相容性，在体内缓慢降解，并且已用于多种TE结构中。在此，报道了包含多孔微通道的嵌入式网络的基于丝绸的TE支架的制造。封闭的多孔微通道支持内皮腔的形成，这是朝着血管生境发展的关键步骤，而微通道周围的多孔支架则支持组织的形成，这是使用人间充质干细胞证明的。与先前的系统相比，这种制造血管化的TE构建体的方法是有利的，后者缺乏孔隙率和生物降解性，或者降解得太快而无法维持组织的结构和功能。这项研究的广泛影响将使系统的研究和开发复杂的，临界尺寸的工程组织成为可能，从再生医学到疾病状态的体外组织模型。

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  • 来源
    《Advanced Functional Materials》 |2013年第27期|3404-3412|共9页
  • 作者

    Lindsay S. Wray; Konstantinos Tsioris; Eun Seok Gil; Fiorenzo C. Omenetto; David L. Kaplan;

  • 作者单位

    Department of Biomedical Engineering Tufts University 4 Colby Street, Medford, MA, 02155, USA;

    Department of Biomedical Engineering Tufts University 4 Colby Street, Medford, MA, 02155, USA;

    Department of Biomedical Engineering Tufts University 4 Colby Street, Medford, MA, 02155, USA;

    Department of Biomedical Engineering Tufts University 4 Colby Street, Medford, MA, 02155, USA;

    Department of Biomedical Engineering Tufts University 4 Colby Street, Medford, MA, 02155, USA;

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